Segmented scaffolds and delivery thereof for peripheral applications

ABSTRACT

Segmented scaffolds composed of disconnected scaffold segments are delivered to an implant site on a delivery balloon. The segments are crimped to the balloon and separated from each other by gaps. When the balloon is inflated the gaps between the disconnected scaffold segments stay constant. Pillowed or banded balloons are used to deliver the segments.

This application is a divisional of U.S. application Ser. No.13/441,756, filed Apr. 6, 2012, the entire contents of which are herebyincorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to methods of treatment of blood vessels withmetallic and polymeric medical devices, in particular, stent scaffolds.

2. Description of the State of the Art

This invention relates to radially expandable endoprostheses, that areadapted to be implanted in a bodily lumen. An “endoprosthesis”corresponds to an artificial device that is placed inside the body. A“lumen” refers to a cavity of a tubular organ such as a blood vessel. Astent is an example of such an endoprosthesis. Stents are generallycylindrically shaped devices that function to hold open and sometimesexpand a segment of a blood vessel or other anatomical lumen such asurinary tracts and bile ducts. Stents are often used in the treatment ofatherosclerotic stenosis in blood vessels. “Stenosis” refers to anarrowing or constriction of a bodily passage or orifice. In suchtreatments, stents reinforce body vessels and prevent restenosisfollowing angioplasty in the vascular system. “Restenosis” refers to thereoccurrence of stenosis in a blood vessel or heart valve after it hasbeen treated (as by balloon angioplasty, stenting, or valvuloplasty)with apparent success.

Stents are typically composed of scaffolding that includes a pattern ornetwork of interconnecting structural elements or struts, formed fromwires, tubes, or sheets of material rolled into a cylindrical shape.This scaffold or scaffolding gets its name because it physically holdsopen and, if desired, expands the wall of the passageway. Typically,stents are capable of being compressed or crimped onto a catheter sothat they can be delivered to and deployed at a treatment site.

Delivery includes inserting the stent through small lumens using acatheter and transporting it to the treatment site. Deployment includesexpanding the stent to a larger diameter once it is at the desiredlocation. Mechanical intervention with stents has reduced the rate ofacute closure and restenosis as compared to balloon angioplasty.

Stents are used not only for mechanical intervention but also asvehicles for providing biological therapy. Biological therapy usesmedicated stents to locally administer a therapeutic substance. Thetherapeutic substance can also mitigate an adverse biological responseto the presence of the stent. A medicated stent may be fabricated bycoating the surface of either a metallic or polymeric scaffold with abioresorbable polymeric carrier that includes an active or bioactiveagent or drug. Polymeric scaffolding may also serve as a carrier of anactive agent or drug by incorporating a drug throughout the scaffoldingmaterial.

The stent must be able to satisfy a number of mechanical requirements.The stent must have sufficient radial strength so that it is capable ofwithstanding the structural loads, namely radial compressive forces,imposed on the stent as it supports the walls of a vessel. Thisstructural load will change as a function of time as the vessel heals,undergoes positive remodeling, or adapts to the presence of the stent.Once expanded, the stent must adequately provide lumen support during atime required for treatment in spite of the various forces that may cometo bear on it, including the cyclic loading induced by the beatingheart. In addition, the stent must possess sufficient flexibility with acertain resistance to fracture.

Stents implanted in coronary arteries are primarily subjected to radialloads, typically cyclic in nature, which are due to the periodiccontraction and expansion of vessels as blood is pumped to and from abeating heart. Stents implanted in peripheral blood vessels, or bloodvessels outside the coronary arteries, e.g., iliac, femoral, popliteal,renal and subclavian arteries, however, can undergo significantnonpulsatile forces and must be capable of sustaining both radial forcesand crushing or pinching loads. These stent types are implanted invessels that are closer to the surface of the body, and may be close tojoints. Because these stents are close to the surface of the body, theyare particularly vulnerable to crushing or pinching loads, which canpartially or completely collapse the stent and thereby block fluid flowin the vessel.

The superficial femoral artery (SFA), in particular, can subject ascaffold to various nonpulsatile forces, such as radial compression,torsion, flexion, and axial extension and compression, which place ahigh demand on the mechanical performance of implants.

Thus, in addition to high radial strength, stents or scaffolds forperipheral vessels such as the SFA, require a high degree of crushrecovery. The term “crush recovery” is used to describe how the scaffoldrecovers from a pinch or crush load, while the term “crush resistance”is used to describe the minimum force required to resist a permanentdeformation of a scaffold.

Stents made from biostable or non-bioerodible materials, such as metals,have become the standard of care for percutaneous coronary intervention(PCI) as well as in peripheral applications, such as the superficialfemoral artery (SFA), since such stents have been shown to be capable ofpreventing early and late recoil and restenosis.

However, in many treatment applications, the presence of a stent in abody is necessary for a limited period of time until its intendedfunction of, for example, maintaining vascular patency and/or drugdelivery is accomplished. Moreover, it is believed that biodegradablescaffolds allow for improved healing of the anatomical lumen since theyallow the vessel to return to its natural state as compared to metalstents, which may lead to a reduced incidence of late stage thrombosis.In these cases, there is a desire to treat a vessel using a polymerscaffold, in particular a bioerodible polymer scaffold, as opposed to ametal stent, so that the prosthesis's presence in the vessel is for alimited duration. However, there are numerous challenges to overcomewhen developing a polymer scaffold, particularly in peripheral bloodvessels, or blood vessels outside the coronary arteries in which a stentis subjected to both radial forces and nonpulsatile forces.Additionally, there are challenges in delivery of polymer scaffolds inperipheral vessels.

SUMMARY OF THE INVENTION

Embodiments of the present invention include a method for delivering asegmented scaffold comprising: providing a delivery balloon comprising aplurality of disconnected scaffold segments arranged end to end andspaced apart by gaps, wherein the segments are crimped to the balloon;and inflating the balloon to radially expand the segments, wherein therelative size of the gaps is constant during and after completeinflation and expansion of the segments.

Embodiments of the present invention include a method for delivering asegmented scaffold comprising: providing a delivery balloon, wherein atleast two disconnected scaffold segments are disposed over the balloonand are spaced apart by gaps, wherein each gap comprises a band ofraised balloon material; and inflating the balloon to radially expandthe segments, wherein the gaps between the segments are maintained to beabout a width of the bands of material during and after completeinflation of the balloon and expansion of the segments.

Embodiments of the present invention include a delivery system for asegmented scaffold comprising: a delivery balloon comprising apre-pillowed band of raised balloon material; and two disconnectedscaffold segments crimped over the balloon separated by the band.

Embodiments of the present invention include a method for delivering asegmented scaffold comprising: providing a delivery balloon comprising aplurality of disconnected scaffold segments arranged end to end suchthat adjacent segments are spaced apart by a gap, wherein the segmentsare crimped to the balloon; and inflating the balloon to radially expandthe segments, wherein the balloon shortens as it is inflated, whereinthe shortening of the balloon reduces the increase in the gap betweenadjacent segments caused by shortening of the segments as they expand

Embodiments of the present invention include a delivery system for asegmented scaffold comprising: a delivery balloon comprising a wallincluding two layers, wherein the layers have different durometerhardness which causes the balloon to shorten when expanded; and twodisconnected scaffold segments crimped over the balloon.

Embodiments of the present invention include a delivery system for asegmented scaffold comprising: a delivery balloon; a band wrapped aroundan axial section of the balloon; and two disconnected scaffold segmentscrimped over the balloon, wherein the rigid band is in a gap between thetwo disconnected scaffold segments, wherein when the balloon is inflatedthe rigid band restricts expansion of the balloon between the scaffoldsections which causes shortening of the balloon as it expands.

Embodiments of the present invention include a method for delivering asegmented scaffold comprising: selecting a gap size between implanteddisconnected scaffold segments of a segmented scaffold; positioning afirst scaffold segment at a first implant site, wherein the firstsegment is at a reduced crimped diameter; deploying the first segment atthe first implant site at an expanded diameter; positioning a secondscaffold segment at a second implant site proximal to the deployed firstscaffold segment, wherein the second segment is at a reduced crimpeddiameter; and deploying the second segment at an expanded diameter,wherein a gap between the deployed first scaffold segment and deployedsecond segment is the selected gap size.

Embodiments of the present invention include a system for deploying asegmented scaffold comprising: a sheath comprising an inner lumen anddistal end with an opening; a delivery balloon disposed within thelumen; a first scaffold segment and a second scaffold segment arrangedend to end, wherein the first segment is distal to the second segmentand is crimped over a balloon, wherein the balloon and segments aremovable along the cylindrical axis of the lumen.

Embodiments of the present invention include a method of delivering asegmented scaffold comprising: selecting a gap size between implanteddisconnected scaffold segments of a segmented scaffold; positioning asheath proximal to implant sites, wherein a first scaffold segment and asecond scaffold segment crimped over a balloon are disposed within thesheath, wherein the first segment is distal to the second segment;extending the first segment out of the sheath; deploying the firstsegment at a first implant site; after deployment of the first segment,positioning the second segment out of the sheath; and deploying thesecond segment at the second implant site, wherein a gap between thedeployed first segment and the deployed second segment is the selectedgap size.

Embodiments of the present invention include a method of delivering asegmented scaffold comprising: selecting a gap size between implantedscaffold segments of a segmented scaffold; positioning a sheath distalto implant sites, wherein at least a second scaffold segment is disposedwithin the sheath, wherein a first scaffold segment is distal to thesecond segment and is crimped over a balloon; deploying the firstsegment at a first implant site; positioning the balloon within thesecond segment; securing the second segment over the balloon; extendingthe second segment out of the sheath to a second implant site proximalto the deployed first segment; and deploying the second segment at thesecond implant site, wherein a gap between the deployed first segmentand the deployed second segment is the selected gap size.

Embodiments of the present invention include a method of delivering asegmented scaffold comprising: positioning a sheath proximal to implantsites, wherein three or more scaffold segments crimped over a balloonare disposed within the sheath; extending a set of at least two of thesegments out of the sheath, wherein at least at least one segmentremains within the sheath; deploying the set of segments at a set ofimplant sites; after deployment of the set of segments, positioning anadditional segment remaining in the sheath outside of the sheath; anddeploying the additional segment at a second implant site, wherein a gapbetween the proximal-most set of deployed segments and the deployedadditional segment is a selected gap size.

Embodiments of the present invention include a method of delivering asegmented scaffold comprising: providing a delivery balloon, wherein twodisconnected scaffold segments are disposed over the balloon and arespaced apart by a gap, inflating the balloon to radially expand thesegments, wherein a width of the gap between the segments is constantduring and after complete inflation of the balloon and expansion of thesegments.

Embodiments of the present invention include a method of delivering asegmented scaffold comprising: providing a delivery balloon, wherein twodisconnected scaffold segments arranged end to end and spaced apart by agap are disposed over the balloon, wherein the segments are crimped tothe balloon; inflating and expanding the balloon to expand the segments,wherein expansion of the segments increases the width of the gap betweenthe segments; and applying an axially directed force to the balloon toshorten the balloon to reduce the width of the gap.

Embodiments of the present invention include a system for deployment ofa segmented scaffold comprising: an outer tubular member; an innerelongate member disposed within the outer tubular member; and a deliveryballoon disposed over at least the inner elongate member, wherein aproximal end of the balloon is attached to the outer tubular member anda distal end of the balloon is attached to a distal end of the innerelongate member, wherein the inner elongate member is axially slideablewithin the outer tubular member, wherein when the balloon is at leastpartially inflated, sliding the inner elongate member proximally causesthe balloon to shorten.

Embodiments of the present invention include a system for deployment ofa segmented scaffold comprising: a delivery balloon; a first scaffoldsegment and second scaffold segment arranged end to end and crimped overthe balloon; at least one spacer member attached to the balloon in a gapbetween the segments, wherein the at least one spacer member isassociated with each of the segments in a manner that maintains aconstant gap size between the segments when the balloon inflates andexpands the segments.

Embodiments of the present invention include a method for deployment ofa segmented scaffold comprising: a delivery balloon and a first scaffoldsegment and second scaffold segment arranged end to end and crimped overthe balloon; inflating the balloon to expand the first and secondsegments, wherein at least one spacer member attached to the balloon andassociated with the segments maintains a constant gap size between thesegments when the balloon inflates and expands the segments.

Embodiments of the present invention include a method for delivering asegmented scaffold comprising: positioning a delivery balloon comprisinga plurality of disconnected scaffold segments arranged end to end andspaced apart by gaps at a treatment site within a blood vessel of apatient, wherein the segments are crimped to the balloon, wherein asurface of the balloon between the gaps comprises a coating including atherapeutic agent; and inflating the balloon to radially expand andimplant the segments at the implant site, wherein the therapeutic agentsreduces restenosis at the implant site at or proximal to the gaps.

Embodiments of the present invention include a system for delivering asegmented scaffold comprising: a delivery balloon; and a plurality ofdisconnected scaffold segments arranged end to end and spaced apart bygaps which are crimped over the balloon, wherein a surface of theballoon between the gaps comprises a coating including anantiproliferative therapeutic agent.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference, and as if eachsaid individual publication or patent application was fully set forth,including any figures, herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts an exemplary stent scaffold.

FIG. 2 depicts an exemplary scaffold pattern which shows schematicallythe forces acting on the scaffold.

FIG. 3A depicts an exemplary scaffold segment of a segmented scaffold.

FIG. 3B depicts a close-up view of a portion of the scaffold segment inFIG. 3A illustrating various features.

FIG. 4 depicts a segmented scaffold composed of a plurality of axialsegments from FIG. 3A.

FIG. 5 depicts scaffold segments of a segmented scaffold mounted over aballoon in a folded configuration.

FIG. 6A depicts a schematic view of a scaffold crimped over a balloonprior to inflation.

FIG. 6B shows the scaffold and balloon of FIG. 6A when the balloon ispartially inflated.

FIG. 6C depicts the scaffold and balloon of FIGS. 6A-B when balloon isfully inflated and expanded.

FIG. 7 depicts an axial projection of an exemplary delivery balloon in adeflated configuration including pre-pillowed bands of balloon material.

FIG. 8A depicts a balloon in a folded condition with three scaffoldsegments crimped over the balloon.

FIG. 8B depicts the balloon-scaffold assembly of FIG. 8A when balloon isin a partially inflated state.

FIG. 8C depicts the balloon-scaffold assembly of FIGS. 8A-B when theballoon is in a completely inflated condition.

FIG. 9 depicts an axial cross-section of a cylindrical balloonpre-pillowing mold.

FIG. 10A depicts an assembly including scaffold segments positioned overa stepped mandrel prior to disposing into a pre-crimper.

FIG. 10B depicts the assembly in FIG. 10A after the scaffold segmentsare pre-crimped.

FIG. 11A depicts a balloon assembly with a balloon in a deflated state.

FIG. 11B depicts the balloon assembly of FIG. 11A with the balloon in aninflated state.

FIG. 12A depicts a delivery balloon in a deflated state with a banddisposed around the balloon at two axial positions.

FIG. 12B depicts the balloon of FIG. 12A in a partially inflated state.

FIG. 12C depicts the balloon of FIG. 12A in a fully inflated state.

FIG. 13A depicts a system for deploying multiple scaffold segments thatincludes three scaffold segments over a balloon disposed within asheath.

FIG. 13B depicts the system of FIG. 13A with the most distal segmentextended out of sheath.

FIG. 13C depicts the system of FIGS. 13A-B with the balloon and segmentoutside the sheath fully expanded.

FIG. 13D depicts the system of FIGS. 13A-C with the second most distalsegment extended out of the sheath.

FIG. 13E depicts the system of FIGS. 13A-D with the second most distalsegment fully expanded.

FIG. 14A depicts a system for deploying multiple scaffold segments of asegmented scaffold at any required spacing with two proximal segments ina sheath over a guide wire and a distal segment outside the sheathcrimped over a balloon.

FIG. 14B depicts the system of FIG. 14A with the distal segment deployedby the inflated balloon.

FIG. 14C depicts the system of FIGS. 14A-B with the balloon deflated anddrawn within the second most distal segment within the sheath.

FIG. 14D depicts the system of FIGS. 14A-C with the second most distalsegment advanced out of the sheath.

FIG. 14E depicts the system of FIGS. 14A-D with the second most distalsegment deployed.

FIGS. 14F-H depict the system of FIGS. 14A-E with the steps illustratedin FIGS. 14C-E repeated to deploy the final desired number of segments.

FIGS. 15A-B depict a system for deploying multiple scaffold segments ofa segmented scaffold.

FIGS. 16A-D depict a system for and method of deployment of two scaffoldsegments with a constant spacing during deployment.

FIG. 17A depicts a half axial cross-sectional view of a delivery systemfor scaffold segments of a segmented scaffold with a pinched balloon inan inflated state.

FIG. 17B depicts the system of FIG. 17A with the balloon shortened.

FIG. 18A depicts a side view of the system of FIG. 17A with the balloonin a deflated state.

FIG. 18B depicts a side view of the system FIGS. 17A-B with the balloonin an inflated state and the segments expanded.

FIG. 18C depicts another side view of the system of FIG. 17B.

FIG. 19A-D depicts a system for and method for deploying scaffoldsegments of a segmented scaffold using spacer clips in gaps betweenscaffold segments.

FIG. 20A depicts a close-up axial cross-sectional view of the gap regionbetween segments of the system of FIGS. 19A-D.

FIG. 20B depicts a close-up overhead view of the gap region betweensegments of the system of FIGS. 19A-D.

FIG. 20C depicts a radial cross-sectional view of the gap region betweensegments of the system of FIGS. 19A-D.

FIG. 21A depicts a photograph of a delivery balloon in a deflated statewith pre-pillowed bands or sections to set scaffold segment spacing onthe balloon.

FIG. 21B depicts a close-up view of a pre-pillowed section of FIG. E1A.

FIG. 22 illustrates the inflation process of a segmented scaffold.

FIG. 23A depicts an implanted segmented scaffold in the Right ExternalIliac in the porcine model.

FIG. 23B depicts a close-up view of a segment which shows radiopaquemarkers in the scaffold segment.

FIG. 24A depicts scaffold segments placed on a stepped mandrel forloading into a crimper to perform a pre-crimping process.

FIG. 24B depicts pre-crimped segments of FIG. 24A upon removal from thepre-crimper.

FIG. 25A shows pre-crimped segments of FIG. 24B loaded onto apre-pillowed balloon.

FIG. 25B shows the finished crimped segments of FIG. 25A.

FIG. 25C is a close up view of the final crimped scaffold of FIG. 25Bshowing pillowing between the segments.

FIG. 26A-B depicts flattened views of two segmented scaffold designs.

FIG. 27 depicts the dislodgment force in lb_(f) for segmented andnon-segmented scaffold designs.

FIG. 28 depicts the post dilate to fracture in mm diameter for segmentedand non-segmented scaffold designs.

FIG. 29 depicts the scaffold diameter acute recoil after deployment forsegmented and non-segmented scaffold designs.

FIG. 30 depicts radial strength in Newton/mm of segmented andnon-segmented scaffold designs.

FIG. 31 depicts the radial stiffness in Newton/mm of segmented andnon-segmented scaffold designs.

FIG. 32 depicts the crush recovery of segmented and non-segmentedscaffold designs.

DETAILED DESCRIPTION OF THE INVENTION

Coronary arteries refer generally to arteries that branch off the aortato supply the heart muscle with oxygenated blood. Peripheral arteriesrefer generally to blood vessels outside the heart. In both coronaryartery disease and peripheral artery disease, the arteries becomehardened and narrowed or stenotic and restrict blood flow. In the caseof the coronary arteries, blood flow is restricted to the heart, whilein the peripheral arteries blood flow is restricted leading to thekidneys, stomach, arms, legs, feet, and brain. The narrowing is causedby the buildup of cholesterol and other material, called plaque, ontheir inner walls of the vessel. Such narrowed or stenotic portions areoften referred to as lesions. Arterial disease also includes thereoccurrence of stenosis or restenosis that occurs after an angioplastytreatment. Although there are probably several mechanisms that lead torestenosis of arteries, an important one is the inflammatory response,which induces tissue proliferation around an angioplasty site. Theinflammatory response can be caused by the balloon expansion used toopen the vessel, or if a stent is placed, by the foreign material of thestent itself.

A stent, a stent scaffold, or scaffold includes a plurality ofcylindrical rings connected or coupled with linking elements. Whendeployed in a section of a vessel, the cylindrical rings are loadbearing and support the vessel wall at an expanded diameter or adiameter range due to cyclical forces in the vessel. Load bearing refersto the supporting of the load imposed by radial inwardly directedforces. Structural elements, such as the linking elements or strutsprimarily serve to maintain stability and connectivity between therings. For example, a stent may include a scaffold composed of a patternor network of interconnecting structural elements or struts.

FIG. 1 illustrates a portion of an exemplary prior art stent or scaffoldpattern 100 shown in a flattened view. The pattern 100 of FIG. 1represents a tubular scaffold structure so that an axis A-A is parallelto the central or longitudinal axis of the scaffold. FIG. 1 shows thescaffold in a state prior to crimping or after deployment. Pattern 100is composed of a plurality of ring struts 102 and link struts 104. Thering struts 102 form a plurality of cylindrical rings, for example,rings 106 and 108, arranged about the cylindrical axis A-A. The ringshave an undulating or sinusoidal structure with alternating crests orpeaks 116 and troughs or valleys 118. The rings are connected by thelink struts 104. The scaffold has an open framework of struts and linksthat define a generally tubular body with gaps 110 in the body definedby rings and struts. A cylindrical tube may be formed into this openframework of struts and links by a laser cutting device that cuts such apattern into a thin-walled tube that may initially have no gaps in thetube wall.

The structural pattern in FIG. 1 is merely exemplary and serves toillustrate the basic structure and features of a stent or scaffoldpattern. A stent such as stent 100 may be fabricated from a polymerictube or a sheet by rolling and bonding the sheet to form the tube. Atube or sheet can be formed by extrusion or injection molding. A stentpattern, such as the one pictured in FIG. 1, can be formed on a tube orsheet with a technique such as laser cutting or chemical etching. Thestent can then be crimped onto a balloon or catheter for delivery into abodily lumen.

The width and or thickness of the struts in a scaffold may be 80 to 300microns, or more narrowly, 100 to 250 microns, 140 to 180 microns, or140 to 160 microns

Semicrystalline polymers such as poly(L-lactide) (PLLA) with glasstransition temperature (Tg) above human body temperature may be suitableas materials for a totally bioresorbable scaffold since they arerelatively stiff and strong at the conditions of the human body.However, they tend to be brittle at these conditions. These polymersystems exhibit a brittle fracture mechanism in which there is littleplastic deformation prior to failure. As a result, a stent fabricatedfrom such polymers can be vulnerable to fracture during use of ascaffold, i.e., crimping, delivery, deployment, and during a desiredtreatment period post-implantation.

Embodiments of the present invention are applicable to endovasculartreatment of coronary and peripheral disease in coronary arteries andvarious peripheral vessels including the superficial femoral artery, theiliac artery, and carotid artery. The embodiments are further applicableto various stent types, such as self-expandable and balloon expandablestents. The embodiments are further applicable to various stent designsincluding scaffolding structures formed from tubes, wire structures, andwoven mesh structures.

In general, the initial clinical needs for a bioresorbable scaffold isto provide mechanical/structural support to maintain patency or keep avessel open at or near the deployment diameter. The scaffold is designedto have sufficient radial strength or vessel wall support for a periodof time. The vessel wall support provided by the stent allows thestented segment of the vessel to undergo healing and remodeling at theincreased diameter. Remodeling refers generally to structural changes inthe vessel wall that enhance its load-bearing ability.

A period of vessel wall support is required in order to obtain permanentpositive remodeling and vessel healing and hence maintenance of vesselpatency. As the polymer of the stent degrades, the radial strength ofthe scaffold decreases and the load of the vessel is graduallytransferred from the scaffold to the remodeled vessel wall. In additionto the decline in radial strength, the degradation of the scaffold alsocauses a gradual decline in the mechanical integrity, i.e., connectivityof struts and the size and shape of the overall scaffold structure. Thestruts gradually resorb and disappear from the vessel.

The amount of movement experienced by a peripheral scaffold in theperipheral artery is greater than what a coronary scaffold experiencesin the coronary artery. A peripheral scaffold can be subjected to a highdegree of flexing, axial elongation/compression, pinching, bending, andtorsion after implantation. Axial stresses on the scaffold can arisefrom the axial compression and extension, flexural stresses are imposedby lateral flexing, crushing forces are imparted by pinching, whilehelical stress can arise from torsional forces.

Such stresses are propagated along the length of the scaffold and canimpart significant forces throughout the scaffold structure. The forcescan cause failure in ring struts, resulting in a decrease or loss invessel wall support provided by the scaffold. Such forces can betransmitted along the length of the scaffold by link struts that connectrings.

Link strut breakage is not inherently deleterious to either performanceor safety. Bench testing and animal study results suggest that scaffoldproperties of radial strength, crush recovery, and crush resistance areprimarily attributable to the mechanical/structural integrity of therings in the scaffold and not the links.

Strut breakage can lead to release of fragments in the blood and tissueirritation from broken strut fragments. Fragment release could result inthrombosis. Broken fragments can be mechanically injurious to the vesselleading to tissue irritation or even vessel dissection and perforation.

FIG. 2 depicts the exemplary scaffold pattern 100 which showsschematically the forces acting on the peripheral scaffold. Line A-Arepresents the cylindrical axis of the stent. The arrows around theedges represent the forces acting on the scaffold during delivery andafter deployment. Arrows 111 represent bending, arrows 112 representradial compression, and arrows 114 represent axial compression. Bendingoccurs during delivery through torturous anatomy and after deployment.

Radially compressive forces on the scaffold are caused by the push backof the vessel walls on the scaffold. Axial compressive forces in the SFAarise due to movement of a leg such as during walking or bending of theleg. In the SFA, the axial compressive forces can be considerable as thevessel is compressed up to 7% or more and relaxed repeatedly up to onemillion cycles/year.

Cracks in the scaffold occur when it is subjected to a sufficiently highforce such as resulting from bending during delivery or repetitiveforces after deployment that cause fatigue. These cracks can cause aloss of radial strength or separation of struts of the scaffold thatdrift downstream of the scaffold.

A crack in the ring strut may cause a reduction or loss of radialstrength, while a crack in the link is less damaging to the scaffold interms of radial strength, crush resistance, and crush recovery. It isbelieved that if the axial forces on the scaffold were reduced, theoccurrence of ring cracks would be significantly reduced. When axialforces through the links to the ring struts are reduced, then thepotential for ring strut fractures are also reduced.

The various embodiments of the present invention are directed toperipheral scaffolds that are subjected to significant nonpulsatileforces upon implantation. Embodiments are further directed to methodsand systems for delivering such peripheral scaffolds. The embodiments ofthe scaffold designs are directed to reducing or eliminated strutfracture and breakage during use of the scaffold.

Various embodiments include a scaffold composed of axial scaffoldsegments that are not connected by link struts. Embodiments of such ascaffold include two or more radially expandable axial scaffold segmentsarranged axially end to end. The axial segments, in particular, axiallyadjacent segments are not connected by any physical structure ormaterial of the scaffold. The axial segments, however, may be indirectlyin contact through another structure such as a support member or asheath. The axial segments may further be connected by structures notpart of structure from which the scaffold segments are formed, such as atube.

In general, upon deployment of the scaffold segments, forces subjectedon one axial segment cannot be transmitted to other axial segmentsthrough linking struts as such forces are by linking struts of ascaffold shown in FIG. 1. The axial segments may be composed of aplurality of interconnected struts. Forces subjected to a segment can betransmitted between struts within the segment, but not between segments.

In some embodiments, the axial segments are composed of one or morecylindrical rings of struts. A cylindrical ring may be composed ofundulating struts having crests and troughs. The cylindrical rings ofstruts that are adjacent in a segment are connected. The rings may beconnected by link struts. Alternatively, the rings may be directlyconnected to one another without link struts. The number of rings in asegment may be one or any number greater than one. In some embodiments,a segment can have 1 or more, 2 or more, 1 to 6 rings, 1 to 3 rings, 2to 6 rings, or 2 or 3 rings.

Upon deployment, the axial segments remain intact for a period of timeand maintain a ring shape at or near the deployed diameter. Since theaxial segments are not connected, they are uncoupled which preventstransmission of axial compression between segments. The decoupled axialsegments retain sufficient radial strength to support the vessel at ornear the deployed diameter. The decoupling of the axial segments reducesstress, for example, from axial compression that causes fracture of ringstruts. The reduced ring strut fracture helps maintain the radialstrength and the crush recovery and resistance to broken off struts ofthe scaffold floating down the vessel as emboli. The decoupling of ringsreduces or prevents propagation of fracture of rings due to bending ofthe scaffold structure along its axis.

In some embodiments, a scaffold with disconnected axial segments can befabricated by forming the axial segments separately. For example, ascaffold pattern can be cut into a thin-walled tube having an axiallength the same as the desired axial segment. Alternatively, a scaffoldcan be fabricated by laser cutting a tube and then axial segments can beformed cutting the scaffold into disconnected axial segments by cuttinglink struts between segments or cutting the link struts between segmentsoff entirely. Unless otherwise specified, scaffold segments or segmentsrefer to disconnected scaffold segments or segments.

The stability of an axial segment may depend on the length of the axialsegment. The stability is inversely related to the length of the axialsection. The susceptibility to fracture from nonpulsatile forces,however, is directly related to the length of the axial section. Thelength of the axial segments should be large enough so that it has adesired stability, while having reduced fracture arising fromnonpulsatile forces.

The radial strength and radial stiffness of a scaffold or scaffoldsegment increases with the degree of connectivity of a scaffold. Thedegree of connectivity refers in part to the number of link strutsbetween rings and the length of the link struts: more link struts andshorter link struts tend to increase strength and stiffness. The stifferthe scaffold, the more susceptible the scaffold is to fracture. In thepresent embodiments, since compressive forces are not transmitted alongan entire scaffold length, the scaffold segments can be made with ahigher connectivity than a scaffold that does not have disconnectedaxial segments.

In the scaffolds such as the one depicted in FIG. 1, the crests of theaxial rings are axially aligned or approximately axially aligned. Thestiffness of the axial segments of such a scaffold can be increased byincreasing the number of link struts between axially adjacent peaks ofadjacent rings. Every pair of aligned peaks between adjacent rings canbe connected, every other pair of aligned peaks can be connected, orevery third pair of aligned peaks can be connected by a link strut.

In some embodiments, the axial segments may be composed of ringsarranged such that the crests in one ring are axially aligned or almostaxially aligned with the troughs in an adjacent ring. The rings areconnected by at least one link strut between an aligned crest andtrough. Stiffness is greatest with a link strut between each alignedcrest and trough. Greater flexibility is introduced by having fewer thanevery aligned crest and trough connected by a link strut. For example,only every other aligned crest and trough can be connected, or onlyevery third aligned crest and trough can be connected by a link strut.Additionally, the length of the link struts in the axial segments can beadjusted to modify the stiffness of the axial segment. Decreasing thelength of the links increases both the radial strength and radialstiffness of the axial segment since the number of rings per segmentlength is maximized. Such a pattern may also be described as a pluralityof rings composed of diamond-shaped elements formed of struts. Theelements of the rings are connected at circumferentially alignedvertices of the diamond-shaped elements. Axially adjacent rings areconnected at axially aligned vertices either by a short link strut or atthe intersection of vertices of elements of adjacent rings.

FIG. 3A depicts an exemplary axial segment 320 viewed in a flattenedconfiguration composed of a plurality of rings of undulating struts withcrests and troughs. Line A-A is the longitudinal axis of the axialsegment. An exemplary ring 322 has crests 324 and troughs 326. As shownin FIG. 3A, every crest in ring 322 is connected to every trough inadjacent ring 328 by a short link strut 330. The arrangement of rings322 and rings 328 forms a plurality of rings 329 of diamond-shapedelements 331 formed of struts. The diamond-shaped elements 331 of therings are connected at circumferentially aligned vertices of thediamond-shaped elements.

Ls is the length of the axial segment. Ls may be 3 to 6 mm, 6 to 8 mm, 8to 10 mm, 10 to 12 mm, or greater than 12 mm in an as cut or asfabricated configuration. Ls increases when the segment is crimped to adecreased diameter and then decreases when expanded from a crimpedconfiguration. Length change is affected by the number of peaks in aring and the width of the diamonds. The length change (increases ordecreases) with the number of peaks and (increases or decreases) withthe width of the diamonds.

FIG. 3B depicts a close-up view of a portion 339 of axial segment 320illustrating various features. As shown in FIG. 3B, Lr is the length ofa ring strut, for example, strut 332 between a crest and trough in aring and Wrs is the width of the ring strut. Ll is the length of shortlink strut 330 that connects crests and troughs of adjacent rings andWls is the width of the link strut. θ is the angle at the longitudinalvertex of the diamond shaped cells, i.e., between struts 332 and 334 ina ring that intersects at a crest or trough. φ is the angle betweenstruts 332 and 336 which are joined by short link strut 330 and adiamond-shaped cell. Hc is the height of the diamond-shaped cell and Wcis the width of the diamond-shaped cell.

θ may be 90 degrees, 90 to 95 degrees, 95 to 100 degrees, 100 to 110degrees, or greater than 110 degrees. θ may be 90 degrees, 85 to 90degrees, 80 to 85 degrees, 70 to 80 degrees, or less than 70 degrees. φmay be 90 degrees, 85 to 90 degrees, 80 to 85 degrees, 70 to 80 degrees,or less than 70 degrees. φ may be 90 degrees, 90 to 95 degrees, 95 to100 degrees, 100 to 110 degrees, or greater than 110 degrees.

Exemplary values for θ and φ are about 70 and 110 degrees, respectively.Values in this range tend to reduce segment shortening from crimping todeployment. Other exemplary values for θ and φ are about 110 and 70degrees, respectively. Values in this range tend to increase segment'sradial strength and crush resistance.

The segments can include radiopaque marker embedded within holes in thescaffold segment to aid in visualization of the implanted scaffold. Insome embodiments, the markers are embedded in holes in the short linkstruts 330 of FIG. 3A. In other embodiments, the markers are embedded inholes in ring struts 332 of FIG. 3B.

When a scaffold segment is crimped, the Ls increases which is caused bybending at the vertices of the diamond-shaped elements. Specifically,when the scaffold segment is crimped, θ decreases and φ increases. Whena scaffold segment is deployed, the Ls shortens which is caused bybending at the vertices of the diamond-shaped elements corresponding toan increase in θ and a decrease in φ.

The segment properties of radial strength and stiffness can be modifiedthrough adjustment of the as-cut geometrical parameters of thediamond-shaped elements. For example, radial strength and stiffness isincreased by increasing Hc which results in a decrease in Wc and alsocorresponds to a decrease in φ and an increase in θ.

In some segment design embodiments, the diamond-shaped elements aresquare-shape or approximately square-shaped in the as-cut condition. Insuch embodiments, φ is the same or approximately the same as θ. Forexample, ABS(φ−θ) may be 2 or about 2 degrees or less than 2 degrees.

In other segment design embodiments, the diamond-shaped elements can betaller or greater in the circumferential direction or, Hc>Wc and φ>θ. Insuch embodiments, the θ−φ may be greater than 2 degrees, 2 to 4 degrees,4 to 8 degrees, greater than 8, about 3 degrees, about 4 degrees, orabout 5 degrees.

L_(l) may be less than 10% or 10% to 20%, 20% to 30%, 30 to 40%, orgreater than 40% of a ring strut length between a crest and a trough.Exemplary link struts may have a length of less than 0.01 in, 0.01 to0.02 in, 0.02 to 0.04 in, 0.04 to 0.06 in, or greater than 0.06 in. Insome embodiments, adjacent rings are connected at an intersection of theopposing crests and troughs such that a length of the link strut iseffectively the width of the intersection.

FIG. 4 depicts a segmented scaffold 340 composed of a plurality of axialsegments 341 to 347, from FIG. 3A. The delivery of a scaffold composedof decoupled or disconnected axial segments can be achieved by disposingthe axial segments over a catheter of delivery balloon. The axialsegments can be arranged end to end and spaced apart on a single balloonor multiple balloons arrange end to end. The axial segments may becrimped over the balloon to a reduced diameter configuration to allowfor delivery of a vascular system to a treatment site.

Generally, stent crimping is the act of affixing a radially expandablescaffold or stent to a delivery catheter or delivery balloon so that itremains affixed to the catheter or delivery balloon until the physiciandesires to deliver the stent at the treatment site. Delivery balloonsmay be compliant, semi-compliant, or noncompliant and are made fromPEBAX, nylon, or other type of common balloon material. Examples of suchcrimping technology which are known by one of ordinary skill in the artinclude a roll crimper; a collet crimper; and an iris or sliding-wedgecrimper. In the sliding wedge or iris crimper, for example, adjacentpie-piece-shaped sections move inward and twist toward a scaffold in acavity formed by the sections, much like the leaves in a cameraaperture.

FIG. 5 depicts a projection of axial segments 351, 352, and 353 disposedover a balloon 350 in a deflated configuration. Axial segments arecrimped tightly over the balloon in a reduced diameter configuration. Acrimped configuration generally may correspond to the inner surface ofthe segments in contact with the outer surface of a balloon. The axialsegments are spaced apart by a distance, size, or width Lg, which is thegap between segments. Lg can change during inflation and deployment ofthe segments to a deployed diameter due to movement of the segments andaxial contraction or shortening of the segments. Lg at deployment shouldbe large enough to avoid interference or contact of the segment endsduring bodily movements. Lg at deployment should be large enough so thatthere is axial stability and the support of the vessel is continuous. Inexemplary embodiments, the segments when deployed are spaced apart by0.5 to 2 mm, or more narrowly, 0.5 to 1 mm, 1 to 2 mm, 2 to 3 mm. Therequired Lg is determined by the anatomy that the segmented scaffoldwill be deployed in to, i.e., in the SFA it will need to be greater thanfor the Iliac where vessel compression and bending are virtually zero.In general, Lg is higher for anatomies with higher vessel compressionand bending.

Factors that influence a desired Lg at deployment include the axialcompression in the vessel, bending of the vessel, and stability inpresence of side branches coming off of a segment of the vessel wherethe scaffold is implanted.

When compressive loads are placed on the scaffold the axial compressionmay occur predominantly between segments. Generally, it is important toallow for the decrease in the spacing of the segments during compressionand loading. Therefore, Lg at deployment should be large enough so thatthe segments do not contact or interfere with each other during axialcompression. The Lg at deployment can be selected to allow for an axialcompression of 7 to 15%, or for example, about 13%.

The bending of a vessel with implanted segments results in a decrease inthe Lg at the concave or inner side of the bend with the gap wideningtoward the convex or outer side of the bend. The segments at the innerside of the bend can interfere or make contact with each other if theinitial gap is not wide enough. The Lg at deployment can be selected toallow for bending of 20 to 30 degrees or less than 30 degrees, or about30 degrees. In this case, a 3 mm gap reduces to 0.8 mm at the inner sideof the gap.

The scaffold segments may be deployed in a vessel that includes a sidebranch and a gap between segments that overlap this side branch. In thiscase, Lg can be the width of the side branch or greater or less than thewidth of the side branch. To maintain axial stability of a segment of asegmented scaffold over a side branch, the length of a segment needs tobe longer that the side branch so that the radially supported length ofthe segment is typically 1.5 times the segment diameter when deployed.This diameter:length ratio can be less than a 1:1 ratio, a 1:1 ratio, a1:1.5 ratio or a 1:2 ratio or greater. The ratio is dependant amongother things on the size of the nonpulsatile forces at the deliverysite. For example, the Lg at deployment can be less than 2 or 3 mm.

The diamond pattern disclosed herein tends to maximize the relativefriction between the vessel wall and the segments. With this and thehigh radial and axial rigidity of the diamond pattern,endothelialization of the segments may be sped up and vessel irritationmay be reduced. With quick endothelialization, the scaffold/vessel wallbecomes a composite structure which in itself enhances the radialstrength and hence crush resistance. With most, if not all of themovement transferred to the gaps between the segments, the designutilizes the natural flexibility of the vessel walls to handle anycompression, bending and torsional movements.

In some embodiments, a single high radial strength and stiff scaffoldsegment, such as described above, may be implanted at an implant site.Implanting a single segment without additional segments may be useful intreatments involving vessels that do not undergo axial compression,torsion, or bending. Examples include the Iliac and Renal artery.

During deployment at a lesion site of a conventional balloon expandablestent or scaffold, the balloons generally start to expand at theproximal and distal ends first, producing a dog bone shape. As pressureis increased, the balloon expands in the center, expanding the scaffoldin the center also. This is illustrated in FIGS. 6A-C. FIG. 6A depicts aschematic view of a stent 360 crimped over a balloon 362 prior toinflation. FIG. 6B shows that as the balloon inflates, proximal end 364and distal end 366 expand first, with a center section between the endsexpanded less or not expanded. FIG. 6C depicts a fully expanded balloonwith the center section expanded as well.

With the segmented scaffold which can include several short scaffolds ona single balloon, the balloon can expand in a similar manner, i.e.,expanding at the proximal and distal ends first, followed by expansionof a center section. Expansion at the ends first has the tendency topush the segments axially towards the center of the balloon whichdecreases the segment to segment gap. The gap may be decreased to thepoint that the segments collide with each other. This movement of theindividual segments axially along the balloon during deployment,therefore, can change the segment to segment gap to an undesirably smallsize which can result in interference of the segments. Additionally, thesegment to segment spacing will not necessarily be the same between allsegments. A reduced gap or zero gap may be acceptable where nonpulsatileforces are virtually zero.

Embodiments of the present invention include delivery systems andmethods that maintain a segment to segment gap between axial segmentsexpanded by a balloon that is consistent during and after completeinflation of the balloon and expansion of the segments. In someembodiments, the gap sizes between all or some of the segments changeduring inflation, however, some of the gaps have the same width even astheir widths change during and after complete inflation and expansion ofthe segments. In other embodiments, some gap sizes are different;however, the relative size of gaps is constant as their widths changeduring and after complete inflation and expansion of the segments.

An aspect of these embodiments is a delivery balloon that maintains theconsistent segment to segment gap size between some or all of thesegments during balloon inflation. Embodiments of the balloon include adelivery balloon including one or more sections or bands of raised orpre-pillowed balloon material around the circumference of the balloon.The raised or pre-pillowed sections of the balloon have an axial widthcorresponding to a desired initial segment to segment gap size. Thesegments are crimped over the balloon such that a pre-pillowed sectionis in a gap between adjacent segments. The distal end of one segment isseparated from the proximal end of the adjacent segment by an axialdistance equal to or slightly greater than the width of the pre-pillowedsection. Pillowed sections in the balloon can also be located adjacentto the proximal end of a proximal-most segment at the proximal end ofthe balloon and adjacent to the distal end of a distal-most segment atthe distal end of the balloon.

In some embodiments, each of the pre-pillowed sections or some of thepre-pillowed sections can have the same axial width. As the ballooninflates and expands the segments, the gap between adjacent segments isthe width of the pillowed sections between these segments. As theballoon inflates and expands the segments, the gaps between segmentsseparated by the pre-pillowed sections remain the same.

In other embodiments, some of the pillowed sections can have differentaxial widths. As the balloon inflates and expands the segments, therelative gap size of gaps between segments separated by pillowedsections that have the different widths remains the same. Thus, eventhough the gap sizes change during inflation, the relative gap sizesremain consistent during inflation and expansion of the segments.

FIG. 7 depicts an axial projection of an exemplary delivery balloon 400in a deflated configuration including pre-pillowed sections 401, 402,403, and 404. Pre-pillowed sections 401, 402, 403 and 404 are bands ofraised balloon material around the circumference of balloon 400.Pre-pillowed sections 401, 402, 403, and 404 have a width Wr.Pre-pillowed sections 401, 402, 403, and 404 have an outside diameter Drand a distance Hr above the surface of the unpre-pillowed surface of theballoon. Pre-pillowed sections 401/402, 402/404, and 404/403 areseparated by a distance Lr.

FIG. 8A depicts balloon 400 in a deflated condition over which threeaxial scaffold segments 406, 408, and 410 are crimped. Each segment hasa length, Ls and outer diameter Ds. Pre-pillowed section 402 is betweensegment 406 and segment 408. Pre-pillowed section 404 is between segment408 and segment 410. The segment to segment gap distance, Lg, betweensegments 406/408 and segments 408/410 are equal to the width Wr of thepre-pillowed sections 402 and 404, respectively. Thus, the distal end ofsegment 406 abuts against the proximal end of pre-pillowed section 402and the proximal end of segment 408 abuts against the distal end ofpre-pillowed section 402. Also, the distal end of segment 408 abutsagainst the proximal end of pre-pillowed section 404 and the proximalend of segment 410 abuts against the distal end of pre-pillowed section404. Also, the proximal end of segment 406 abuts against the distal endof pre-pillowed section 401 and the distal end of segment 410 abutsagainst the proximal end of pre-pillowed section 403.

The outer diameter Ds of the segments is greater than the outsidediameter Drof the pre-pillowed sections. Ds may be 1 to 5%, 5-10%, orgreater than 10% more than Dr. Ds may also be the same as or about thesame as Dr.

FIG. 8B depicts the balloon-scaffold assembly of FIG. 8A when balloon400 is in a partially inflated state. As shown in FIG. 8B, the proximalportion and distal portions of balloon 400 are inflated first and acenter portion is not inflated. The inflation of the proximal and distalportions of balloon 400 expands a proximal section of segment 406 and adistal section of segment 410. A distal section of segment 406, proximalsection of segment 410 and segment 408 remain in a crimped state.

FIG. 8C depicts the balloon-scaffold assembly of FIGS. 8A-B when theballoon 400 is in a completely inflated condition. As shown in FIG. 8C,segments 406, 408, and 410 are in fully expanded states due to inflationof the balloon. The length Ls of each segment has decreased due theexpansion. The width, Wr, of the pre-pillowed sections 402, 404increased during the expansion, and thus is larger than Wr in thedeflated configuration. During the expansion to the fully expandedstate, the segment to segment gap distance Lg is maintained to be theincreasing width Wr of the pre-pillowed sections. Thus, gap distancebetween segments 406/408 and 408/410 remains the same during expansion.

The pillowed sections of the balloon can be made by a pre-pillowingprocess which includes applying heat and pressure to a balloon whileallowing bands of balloon material to expand to a greater degree (i.e.,diameter) than the remainder of the balloon. Applying heat results inraising the temperature above ambient, 20 to 30 deg C., of the wholeballoon, only the balloon material of the bands, or only a localizedregion around the bands. Applying heat to the band or band regions onlylimits any negative effects the heat may have on the balloon materialmechanical properties. The remainder of the balloon can be restrainedfrom expansion completely or allowed to partially expand to a lesserdegree than the bands.

Delivery balloons are typically loaded onto a catheter in a deflated,folded configuration. The heat and pressure may be applied when theballoon is an unfolded state or folded state. Therefore, thepre-pillowing process can be performed as part of the balloon foldingprocess or as a separate step after the balloon folding process.

The heat and pressure may be applied when the balloon is in a deflatedstate, partially inflated state, or completely inflated state. For anoncompliant balloon, compete inflation may correspond to expanding theballoon to a maximum size without elastic or plastic deformation of theballoon material. The heat and pressure may cause the balloon materialin the bands to plastically deform, while the material in the remainderof the balloon plastically deforms not at all or to a lesser degree thanthe balloon material in the bands.

When the pre-pillowing process is performed as part of the balloonfolding process, the balloon may be partially or completely inflated andheated while allowing bands of balloon material to expand to a greaterdegree (i.e., diameter) than the remainder of the balloon. The expansionof the bands may correspond to plastic deformation.

The pre-pillowing process can be performed on a folded balloon in apartially or completely deflated state and includes heating whileallowing bands of balloon material to expand to a greater degree (i.e.,diameter) than the remainder of the balloon. The expansion of the bandsmay also correspond to plastic deformation. After the balloon materialis expanded, the temperature is reduced to ambient and any inflatedportions of the balloon are deflated, in particular, the bands.

The pre-pillowing process may be incorporated into the initial balloonshaping process. In this case, as the balloon is blown into a mold thatforms the outside diameter of the balloon, the pre-pillow shape is alsoformed in the same process.

A balloon may be pre-pillowed by using a mold having a cylindricalcavity defined by walls having a first inside diameter. The mold hascylindrical recesses for forming the bands of pre-pillowed balloonmaterial with a second inside diameter larger than the first insidediameter. A balloon is inserted into the mold and heat and pressure areapplied inside the balloon. The first inside diameter may be the same orslightly larger to allow a slip fit of the balloon in the mold. The heatand pressure cause the balloon material at the recesses to expand intothe recess which may expand against the walls of the recesses. Theapplied pressure is removed and the balloon is cooled or allowed to cooland then removed from the mold.

FIG. 9 depicts an axial cross-section of a cylindrical balloonpre-pillowing mold 420. Mold 420 has a cylindrical cavity 422 with axialsections with an inner diameter Dm and cylindrical recesses 421 with aninner diameter Dr and axial width Wr. The axial sections with innerdiameter Dm are defined by walls 424 and the recesses by walls 426. Afolded balloon with an outside diameter the same as or slightly lessthan Dm is disposed within cavity 422. The balloon is heated and thepressure is increased within the mold. The balloon sections located atrecesses 421 expand within the recesses. These balloon sections mayexpand against walls 426 of recesses 421, creating raised bands ofpre-pillowed balloon material with outer diameter Dr and width Wr.

The balloon pressure may be between ambient pressure to 40 psi, 40 to 80psi, 80 to 120 psi, 120 psi to 180 psi, or greater than 180 psi. Thetemperature of the heated mold or the temperature of the balloon duringheating may be 25 to 40 deg C., 40 to 60 deg C., 60 to 80 deg C., 80 to100 deg C., or greater than 100 deg C. The balloon may be heated for 1to 3 min, 1 to 5 min, 3 to 5 min, 5 to 8 min, or greater than 8 min. Theballoon mold may be cooled actively with a cooled gas or allowed to coolat ambient temperature. The cooling time can be 1 to 3 min, 1 to 5 min,3 to 5 min, 5 to 8 min, or greater than 8 min. Typical parameters for apre-pillowing process are given in Table 1 below.

TABLE 1 Typical parameters for a balloon pre-pillowing process. Heatingtemperature 80° C. Air pressure to balloon 175 psi Heating time 5minutes Cooling time 5 minutes

The scaffold segments may be crimped tightly on a delivery balloon usinga crimping apparatus such as an iris crimper. The crimping process mayinclude 2 stages, a pre-crimp process and a final crimp process. In thepre-crimp process, the diameter of the scaffold segments are reduced toan intermediate diameter prior to loading the scaffold segments on theballoon. The reason for the pre-crimp process is to reduce the size ofthe scaffold segments to allow greater accuracy of loading the segmentson a balloon.

The scaffold segments in an as-fabricated condition are placed over amandrel and arranged end to end. The scaffold segments are spaced apartaxially at a distance such that when the segments are reduced to thepre-crimp diameter the segments do not make contact with each other. Forexample, the scaffold segments are placed over a stepped mandrel. Themandrel with the scaffold segments is loaded into the pre-crimper, forexample, an iris crimper and crimped to the pre-crimp diameter. Thepre-crimped scaffold segments may further be placed inside a protectivesheath disposed in a outer surface of the each scaffold segment.

FIG. 10A depicts an assembly 430 including scaffold segments 438positioned over a stepped mandrel 432. Stepped mandrel 432 has largerdiameter sections 434 that step down to smaller diameter sections 436.Scaffold segments 438 are disposed over smaller diameter sections 436.The stepped mandrel with the loaded scaffold segments is placed into thejaws of the crimper. Once the crimper jaws have made contact with thescaffold segments the stepped mandrel is removed and replaced with ahooked mandrel (see FIG. 24B) After the crimping process the crimperjaws open up and the hooked mandrel is used to remove the scaffoldsegments from the crimper. Scaffold segments 438 have a reduced diameterand a longer axial length in the pre-crimped state.

The crimping of the segments from the initial diameter to the finaldiameter may be performed in two or more steps, where each stepcorresponds to crimping to an intermediate diameter between the initialand final crimped diameter. Each diameter reduction can include a dwellperiod before the next diameter reduction step. Additionally, thescaffold segments may be heated during the crimping process to increasethe flexibility of the scaffold segments, which is expected to reducefracturing in the scaffold during crimping.

Table 2 shows exemplary pre-crimper settings for crimping 0.30 indiameter scaffold segments to a final crimp diameter of 0.08 in. Thecrimper head temperature is about 48 deg C. and the inside diameter ofthe protective sheath is 0.125 in.

TABLE 2 Pre crimper settings Diameter (in) Dwell (s) Speed (in/s) 0.31000 0.300 0.2650 30 0.005 0.2100 30 0.005 0.2200 1 0.005 0.1600 30 0.0050.1300 30 0.005 0.0800 60 0.005

The pre-crimped segments are removed from the pre-crimper with a hookedmandrel. The segments are then placed into a protective sheath. Thesheathed scaffolds may then be stored until the final crimping process.

The application of a therapeutic coating to the scaffold segments may beperformed prior to the pre-crimping step. Alternatively, to limitcoating damage, the coating step can be performed after the pre-crimpprocess.

The pre-crimped segments may then be loaded onto a pre-pillowed ballooncatheter with pre-pillowed section, as described above. The segments areplaced over the balloon between and next to the pillowed sections. Thesegments and balloon are then crimped down to about 0.0600 in withpressure applied at multiple steps with a dwell period between steps toachieve segment retention on the balloon. Pressure may be applied to theballoon during the final stages of the crimp process to enhance thescaffold retention to the balloon in the crimped state. When thecatheter is removed from the crimper a protective sheath is placed overthe scaffold segments.

Table 3 shows typical final crimper settings for crimping pre-crimped0.125 in diameter scaffold segments to a final crimp diameter of 0.06in. The crimper head temperature is 48 deg C. and the diameter of theinner protective sheath is 0.092 in. The crimping pressure used was 100psi.

TABLE 3 Final crimper settings Pressure Diameter Dwell Speed Hold Time(in) (sec) (in/sec) (sec) Interrupt 0.1100 20 0.050 5 Yes 0.1150 2 0.3000 No 0.1100 30 0.005 30 No 0.1000 30 0.005 30 No 0.0650 60 0.001 50 No0.0625 30 0.001 0 no 0.0610 30 0.001 0 no 0.0600 255 0.001 0 no

As discussed in the above embodiments, the segment to segment gap of asegmented scaffold changes as the segments are expanded to a deployeddiameter. Deployment of a segmented scaffold with pre-pillowed segmentsprovides for a consistent segment to segment gaps. However, even thoughthe gaps between segments can be the same due to the pre-pillowedsections, the gaps still increases with deployed diameter. The increasein the segment to segment gap with deployment can become undesirablylarge.

Further embodiments of the present invention include methods and systemsfor deploying segmented scaffolds that have a predetermined gap at fulldeployment of the segmented scaffold. The predetermined gap may besmaller than that obtained by expansion of axial segments over a balloonof constant length.

Conventional delivery balloons are designed to stay the same lengthduring inflation and expansion. This allows the scaffold to be deployedwith minimal distortion to the scaffold. Certain embodiments of thepresent invention include deployment of a segmented scaffold with adelivery balloon that reduces the increase in the gap size betweensegments when the balloon is inflated and expands the scaffold.

In some embodiments, a segmented scaffold may be delivered by a balloonthat shortens as it expands. A plurality of disconnected scaffoldsegments are crimped to a shortening balloon with the segments arrangedend to end. Adjacent segments are spaced apart by a gap. The balloon isinflated which radially expands the axial segments and the balloonshortens as it inflates and expands. The balloon length in the fullyexpanded state can be 90 to 95%, 85 to 90%, 80 to 90%, or less than 80%of the diameter of the balloon in the deflated state. The shortening ofthe balloon can partially or completely counteract the shortening of thesegments as they increase in diameter which reduces the growth of thegap. The rigidity of the segments can minimize distortion of thesegments.

FIG. 11A depicts a balloon assembly 500 that includes a balloon 501 in adeflated state with a length Lb. Three scaffold segments 502, 504, and506 are crimped over balloon 501 end to end with a gap 508, with alength Lg, between segments 502 and 504 and a gap 510 between segments504 and 506. When balloon 501 inflates and expands 512, Lb decreases.FIG. 11B depicts balloon 501 in its fully expanded state and its length,Lb, has decreased. The segments have been expanded and their length, Ls,has decreased. However, the shortening of balloon 501 has counteractedthe shortening of the segments, so Lg between the segments is the samein the expanded state.

A delivery balloon that shortens as it inflates can have a wallincluding or made of two or more layers of material. At least two of thelayers can have different properties, such as modulus or durometerhardness. For example, the wall can be made of two or more layers ofPebax®, a polyether block amide made by Arkema, which causes the balloonto shorten when expanded.

The different layers may have different preferential polymer chainorientation. The layers of the balloon walls can be treated to inducepreferential orientation in a specific direction to provide theelasticity and rigidity without being prematurely ruptured duringdeployment. For example, at least one layer may have polymer chainspreferentially radially aligned so that the balloon can withstand highinflation pressures. Another layer could have polymer chains alignedpreferentially in the longitudinal direction. Preferentiallylongitudinal orientation would reduce, inhibit, or minimize longitudinalstretch of the balloon perimeter as the balloon inflates. After theballoon unfolds and continues to expand, it will get shorter as thelongitudinal perimeter increases in diameter.

In another embodiment, a balloon that shortens as it expands has a ringor band wrapped around the circumference of an axial section of theballoon between the scaffold segments crimped over the balloon. When theballoon is in a deflated condition, the inner diameter of the band maybe the same or slightly larger than the outer diameter of deflatedballoon so that the band is tightly fit over the balloon. The band maybe fit tightly enough so that it does not move axially along theballoon. Alternatively, when the balloon is in a deflated condition, theinner diameter of the band may be less than the outer diameter ofdeflated balloon so that the band squeezes the balloon and reduces thediameter of the balloon at the location of the band. For example, theband can reduce the diameter by less than 5%, 5 to 10%, 10 to 20%, 20 to30%, or more than 30%.

When the balloon is inflated, the band inhibits expansion of the balloonbetween the scaffold sections causing shortening of the balloon as itexpands. A balloon that includes three or more segments can includebands in one or more of the gaps between the segments.

The band can be made of the any number of biocompatible materials. Theband may be made of a rigid material that does not expand radially whenthe balloon inflates. For example, the band may be made of abioabsorbable polymer such as PLLA or a PLLA-based polymer.Alternatively, band may be made of a metal such as stainless steel.Alternatively, the band can be made of a material that is flexible orelastomeric so that the material can expand radially when the balloon isinflated while still restricting expansion of the balloon as thelocation of the band. For example, flexible materials includepolycaprolactone, polydioxanone, or a biocompatible crosslinked rubber.

As the balloon inflates, the rings restrict the balloon expansion at itsaxial location in the gaps between the segments. The balloon expands inthe axial portions next to the bands which results in expansion of thesegments. The localized restriction or reduction of expansion in thegaps causes the balloon to shorten as the diameter of the balloonincreases in the adjacent axial sections that are not restricted. As aresult, the increase in the segment spacing is reduced. The segmentspacing can remain constant during inflation or be reduced during theinflation.

FIG. 12A depicts a delivery balloon 520 with rigid bands 522 and 524disposed around balloon 520 at two axial positions. Scaffold segmentscan be crimped over balloon 520 between bands 522 and 524 and to theleft of band 522 and to the right of band 524. FIG. 12B depicts balloon520 in a partially inflated state and FIG. 12C depicts balloon 520 in afully inflated state. As shown in both FIGS. 12B and 12C, bands 522restrict the expansion of balloon 520 since there is a minimum in thediameter of the balloon at the bands. On either side of the bands, thereis a tapered portion 526 of the balloon in which the balloon diameterincreases from the minimum at the band and increases to a maximumexpanded portion 524.

The band width should be wide enough so as not to cut into the balloonas it expands and is stressed locally at the bands. Band widths of 0.02in to 0.20 in and more specifically about 0.06 in can be used. The bestuse of the band is as a spacer for separating and setting the crimpedsegment spacing so as to achieve the desired deployed spacing gap. Thisgap will be dependent on the amount the balloon shortens and the amountthe segments shorten. Preliminary experiments to date indicate that aspace between balloon segments can be shortened by ˜1.5 mm when expandedto 6 mm diameter. Balloons can be from 20 mm long to 120 mm long orlonger, depending on the number of segments to be delivered. The balloondiameters for delivery in the SFA are typically 5 to 7 mm, but thediameter may be from less than 3 mm, 3 mm to 10 mm, or greater than 10mm. Balloon shortening is dependent on balloon material, balloon foldedand expanded diameters, band width and diameter, number of bands andtheir spacing along the balloon length.

In an alternative embodiment, segments can be crimped over individualballoons arranged end to end over a catheter. In another alternativeembodiment, a balloon can include individual balloon chambers withtapered portions between each chamber. The tapered portions shorten asthe balloon is expanded.

In further embodiments, scaffold segments can be deployed in sequencesuch that the gap between adjacent deployed scaffolds is a selected gapsize. In particular, such embodiments include selecting a gap sizebetween implanted scaffold segments of a segmented scaffold. The firstscaffold segment is positioned at an implant site and is at a reducedcrimped diameter. The first segment is deployed at the implant site atan expanded diameter. A second scaffold segment is then positioned at animplant site proximal to the deployed first segment in a reduced crimpeddiameter. The second segment is deployed at an expanded diameter in sucha way that the gap between the deployed first scaffold segment anddeployed second scaffold is the selected gap size. A third, fourth, orany number of segments can be deployed by repeating the proceduredescribed above. The space between each pair of scaffolds can be anydesired or required any gap size.

In the embodiments of sequential deployment, two segments can bedeployed at any required spacing. Radiopaque markers on the segments canmake he segments visible in X-ray imaging, so a physician can use theimaging to position each segment relative to the previously deployedsegment. The physician has maximum versatility in positioning thesegments by deploying segments at different spacing and at differentlocations. For areas with high calcification, segments can be deployedwithin other segments.

A system for deploying scaffold segments sequentially can include asheath with an inner lumen and distal end with an opening and one ormore delivery balloons disposed within the lumen. The system can furtherinclude a first scaffold segment and a second scaffold segment arrangedend to end crimped over the one or more balloons such that the balloonsand scaffold segments are slidable or movable along the longitudinalaxis within the lumen.

A method of delivering a segmented scaffold with such a system includesselecting a gap size between implanted scaffold segments of a segmentedscaffold. The sheath including the balloon and scaffold segments ispositioned distal to implant sites for scaffold segments. The firstscaffold segment is distal to the second segment. The balloon andscaffold segments are slid distally through the inner lumen of thesheath to extend the first scaffold segment out of a distal opening ofthe sheath. The first scaffold segment is then deployed at a firstimplant site by inflating and expanding the balloon outside the distalopening of the sheath. After deployment of the first scaffold segment,the second scaffold segment is slid distally through the inner lumen toextend the second scaffold segment out of the distal opening to a secondimplant site proximal to the deployed first scaffold segment. The secondscaffold segment is deployed at the second implant site. A gap betweenthe deployed first scaffold segment and the deployed second scaffoldsegment is the selected gap size.

FIGS. 13A-E depict a system 530 and method for deploying multiplescaffold segments of a segmented scaffold sequentially at any requiredspacing between any of the segments. FIG. 13A shows that system 530includes a sheath 532 with an inner lumen 534 and an inner surface 536.A balloon 538 is disposed within lumen 534. Scaffold segments 540, 542,and 544 are spaced apart and crimped over balloon 538 inside of lumen536. The inner diameter of sheath 532 may be the same or slightly largerthan the outer diameter of the crimped scaffold segments.

As shown in FIG. 13B, balloon 538 and the segments are slide distallythrough inner lumen 534 until the most distal segment, segment 544, isextended out of sheath 532 through distal opening 533 as shown by arrow546. Alternatively, the system can be delivered to the deployment sitewith segment 544 already extended distally of the sheath 532.

As shown in FIG. 13C, balloon 538 is inflated and the section 538A ofballoon 538 outside of sheath 532 expands, which expands and deployssegment 544. Sheath 532 prevents expansion of the section 538B ofballoon 538 under segments 540 and 542 from expanding. In alternative,embodiments, the diameter of sheath 532 is greater than the outerdiameter of the segments and balloon 538 can expand partially inside ofsheath 532, which partially expands segments 540 and 542. For example,the inside diameter of sheath 532 can be 110 to 120%, 110 to 150%, or120 to 150% of the outer diameter of the segments inside the sheath,which allows expansion of the segments to the inner diameter of thesheath 532.

FIG. 13D shows that after deployment of segment 544, balloon 538 isdeflated and sheath 532 is retracted, as shown by arrows 548, from oversegment 542. Segment 542 is advanced and positioned proximal to deployedsegment 544.

As shown in FIG. 13E, balloon 538 is then inflated and section 538C ofballoon 538 outside of sheath 532 expands, which expands and deployssegment 542. Sheath 532 prevents expansion of the section 538D ofballoon 538 under segment 540. Segment 542 is positioned prior to itsdeployment relative to segment 544 so the gap 550 between segments 542and 544 after deployment is a desired or selected gap size. The processmay be continued to deploy segment 540 and any number of additionalsegments with desired gap sizes between deployed segments.

Another embodiment of a system for deploying a segmented scaffold insequence includes a sheath with a first scaffold segment and a secondscaffold segment. In this embodiment, the first scaffold segment isdistal to the second scaffold segment and only the first scaffoldsegment is crimped over the balloon. The first scaffold segment andballoon are axially slidable relative to the second scaffold segment.

When the first scaffold segment is positioned outside the sheath, thefirst scaffold segment is delivered by inflating and expanding theballoon at a first implant site. After deployment of the first scaffoldsegment, the balloon is deflated and then slid proximally into the innerlumen of the sheath within the second scaffold segment. The secondscaffold segment is then secured over the balloon. The balloon can besecured through a slight inflation of the balloon while still inside ofthe sheath. The second scaffold segment secured over the balloon is thenslid distally through the distal opening out of the sheath to a secondimplant site proximal to the deployed first scaffold segment anddeployed at the second implant site by the balloon. A gap between thedeployed first scaffold segment and the deployed second scaffold is theselected gap size. Additional segments inside the sheath can bedelivered by repeating the process described.

FIGS. 14A-H illustrate a system 550 and method for deploying multiplescaffold segments of a segmented scaffold sequentially at any requiredspacing. FIG. 14A shows that system 550 includes a sheath 552 with aninner lumen 554 with an inner surface 555. Scaffold segments 560 and 562are positioned over inner sheath 556 within lumen 554 of sheath 552. Aproximal end of scaffold segment 560 is positioned against a hard stop558. The inner diameter of sheath 552 may be the same or slightly largerthan the outer diameter of the scaffolds. Scaffold segment 564 ispositioned distal to scaffold segment 562 outside of sheath 552. System550 can be delivered to the implant site in the configuration shown orwith scaffold segment 564 and balloon 566 within sheath 552. In thiscase, once sheath 552 is positioned proximal to an implant site,scaffold segment 564 is extended out of sheath 552 or sheath 552 isretracted so that scaffold segment is outside of sheath 552.

As shown in FIG. 14B, scaffold segment 564 is deployed to a largerdiameter by inflation and expansion of balloon 566. The recoil caused byself expanding properties of the segments inside of the sheath will helphold undeployed segments inside sheath 552.

Referring to FIG. 14C, after deployment of scaffold segment 564, balloon566 is deflated and drawn or slid back relative to scaffold segments 560and 562. Balloon 566 is drawn within scaffold segment 562 and sheath 552is retracted. Scaffold segment 562 is secured onto balloon 566 which canbe performed by inflating balloon 566 slightly while scaffold 562 isstill within sheath 552.

Referring to FIG. 14D, balloon 566 is advanced out of sheath 552 towarddeployed segment 564 and positioned adjacent to it. FIG. 14E showsballoon 566 inflated and expanded, which deploys segment 562 at aselected spacing from segment 564.

The process of FIGS. 14C-E is repeated to deploy the final segment 560at a desired spacing from segment 562, as shown in FIGS. 14F-H. Theprocess can continued until any desired number of segments has beensequentially deployed at the desired spacings. When all the segmentshave been deployed the balloon and sheath can be retracted and removedfrom the patient.

The embodiments in FIGS. 13A-E and 14A-H provide a physician withmaximum versatility in deploying segments at different spacing and atdifferent locations. In some embodiments, segments can be deployedwithin a previously deployed segment. This may be useful in vessel areaswith high calcification. For example, in FIGS. 14D-F, segment 562 can beadvanced within segment 564 and deployed within segment 564.

In further embodiments, two or more segments can be deployedsimultaneously in a vessel by one long balloon and one or moreadditional segments can be deployed sequentially after their deployment.The one or more additional segments can be deployed by the same balloonor by a different balloon. FIG. 15A depicts a system 570 and method fordeploying multiple scaffold segments of a segmented scaffold. In FIG.15A, system 570 includes a sheath 572 with an inner lumen 573 and aninner surface 575. Scaffold segments 576, 578, and 580 are arranged endto end and positioned outside or distal of sheath 572. Segments 576,578, and 580 are crimped over balloon 582 which is in a deflatedcondition. Balloon 582 extends proximally into sheath 572. Scaffoldsegment 574 is positioned over balloon 582 within sheath 572. As shownin FIG. 15B, balloon 582 inflates and expands outside of sheath 572which deploys segments 576, 578, and 580 within a vessel. Sheath 572prevents inflation of balloon 582 within sheath 572. After deployment,balloon 582 is deflated and segment 574 is advanced out of sheath 572.Segment 574 can then be deployed with balloon 582 with a selectedspacing from segment 576. This spacing may be from 1-2 mm, 2-5 mm oreven in a different location within the vessel.

In some embodiments, a constant segment to segment spacing is maintainedduring and after simultaneous deployment of only two scaffold segments.A band of raised balloon material in the gap, as disclosed herein,maintains the constant width of the gap between the segments.

FIG. 16A depicts a system 590 including a deflated balloon 594 that ispositioned within a vessel lumen by a guide wire 592. Scaffold segments596 and 598 are crimped over balloon 594. Segments 596 and 598 arespaced apart by a gap. A band 595 of raised or pre-pillowed balloonmaterial is in the gap. The gap width, Lg, is the same as the width ofband 595.

As shown in FIGS. 16B-C, as the balloon inflates, it takes on a dog boneshape in which ends 594A and 594B of balloon 594 inflate first and alsoexpand the corresponding ends of segments 596 and 598 first. Segments596 and 598 shorten as they expand, however, they are pushed against theband of pre-pillowed balloon material. As the balloon expansioncontinues, the segments shorten and slide on the balloon to maintain aconstant center spacing. FIG. 16D depicts balloon 594 completelyinflated with segments 596 and 598 fully expanded and deployed. The gapwidth, Lg, has remained constant during inflation and deployment of thesegments.

In further embodiments, the gap between deployed segments can beadjusted after partial deployment by shortening the balloon. In suchembodiments, after partial deployment of scaffold segments throughexpansion of a balloon, a proximally directed force is applied to theballoon to shorten the balloon to reduce the width of the gap betweenthe segments to a desired gap width. The partially inflated balloon caninclude a pinched or necked down region between the segments that has areduced diameter. The force causes the balloon to fold into itself atthe pinched region to allow the balloon to shorten and reduce the widthof the gap.

A system for performing such a method can include an outer tubularmember and an inner elongate member disposed within the outer tubularmember. A delivery balloon is disposed over at least the inner elongatemember. A proximal end of the balloon is attached to the outer tubularmember and a distal end of the balloon is attached to a distal end ofthe inner elongate member. The inner elongate member is axiallyslideable within the outer tubular member. When the balloon iscompletely or at least partially inflated, sliding the inner tubularmember proximally causes the balloon to shorten.

FIG. 17A depicts a half axial cross-sectional view of a delivery system600 including a pinched balloon in an inflated state with a proximalballoon section 606 and a distal balloon section 608. Expanded scaffoldsegments 610 and 612 are over balloon sections 606 and 608,respectively. The balloon has a pinched or necked down region 607 with areduced diameter separating proximal balloon section 606 and distalballoon section 608.

Delivery system 600 further includes an outer member 602 disposed overan inner member 604. An inflation pressure applied into inflation lumen605 between inner member 604 and outer member 602 inflates the balloon.A distal end 603 of proximal balloon section 606 is attached to outermember 602. A distal end 609 of distal balloon section 608 is attachedto inner lumen 604. Inner member 604 is proximally slideable withrespect to outer lumen 602, Referring to FIG. 17B, inner lumen 604 isslid or moved proximally with respect to outer member 602, as shown byan arrow 614. The balloon also slides or moves proximally due to aproximal force applied to distal balloon section 608 by inner member 604as it slides. The proximal sliding of the balloon shortens the balloonand causes proximal and distal balloon sections to fold into each otherwhich create folds 614, which shortens the gap between segments 610 and612.

FIGS. 18A-C depict a side view of system 600 of FIGS. 17A-B. FIG. 18Ashows system 600 with the balloon in a deflated state. Pinched or neckeddown region 607 has a reduced diameter compared to proximal balloonsection 606 and distal balloon section 608. As shown in FIG. 18B, thegap width or spacing, Wg, increases between segments 610 and 612 afterinflation or partial inflation and expansion or partial expansion of theballoon. FIG. 18C depicts system 600 after shortening the balloon byproximally sliding inner member 604. The sliding decreases the gap orspacing between segments 610 and 612 and creates folds 614.

In further embodiments, the spacing between scaffold segments duringexpansion can be maintained at a desired constant gap size or width witha spacer member. In such embodiments, a spacer member is attached to aballoon in a deflated state in a gap between segments. The spacer memberis associated with each segment. When the balloon inflates and expandsthe scaffold segments, the spacer member maintains a constant gap sizebetween the segments.

FIG. 19A depicts a system 620 including a deflated balloon 624 that ispositioned within a vessel lumen by a balloon catheter 622. Scaffoldsegments 626, 628, and 630 are crimped over balloon 624. Segments 626and 628 and segments 628 and 630 are spaced apart by gaps, with a widthWg. Spacer clips 632 positioned in the gap between 626 and 628 andspacer clips 634 are positioned in the gap between 628 and 630. Spacerclips 632 and 634 are distributed around the circumference of balloon624 in the respective gaps.

Spacer clips may be made of a metal or a polymer. For example, thespacer clips can be made of a biodegradable polymer, which may be thesame as scaffold segment polymer. They may also be made ofpolycarbonate, stainless steel, or nitinol.

Spacer clips 632 and 634 are attached to balloon 624 and are alsoassociated with segments on either side of the spacer clips. Spacerclips 632 and 634 are described in detail in FIGS. 20A-C.

Balloon 624 inflates and expands segments 626, 628, and 630. FIG. 19Bdepicts system 620 after balloon 624 is inflated and the segments areexpanded. During expansion of the segments, spacer clips 632 maintainthe gap width at Wg between segments 626 and 628 and spacer clips 634maintain the gap width at Wg between segments 628 and 630 due to theassociation of the clips with adjacent segments. Spacer clips 634 canmaintain the gap between segments 628 and 630 at width different fromthat of segments 626 and 628. The segment lengths decrease duringexpansion, however, the spacer clips maintain a constant gap widthbetween segments. If the distal set of clips are attached to the balloonand the other sets of clips are free to float on the balloon, as theballoon expands and the segments shorten, the segments will slide alongthe balloon towards the balloon attached set of clips, thus maintainingthe segment to segment spacing.

As shown in FIG. 19C, after deployment of the segments, balloon 624 isdeflated. The deflation causes the diameter of the balloon to decrease.As balloon 624 deflates spacer clips 632 and 634 disassociate or arepulled away from the segments and remain attached to the balloon. FIG.19D shows balloon 624 is retracted from the deployed segments afterdeflation.

FIG. 20A depicts a close-up axial cross-sectional view and FIG. 20Bdepicts an overhead view of the gap region between segments 626 and 628which shows an exemplary structure spacer clip 632 and association withadjacent segments. Spacer clip 632 has a portion 632A in the gap betweenstruts 626A of segment 626 and struts 628A of segment 628. Portion 632Ais attached to surface 636 of balloon 624. Portion 632A may be attachedto balloon surface 636, for example, by laser bonding 638 oralternatively with an adhesive.

Spacer clip 632 has arms 632B which extend along the gap to struts 626Aand 628B. Arms 632B have a bent or hooked portion 632C which engage theside walls of a crest of the struts of the segments on the side oppositeto the gap, for example, crest 626B, as shown in FIG. 20B.

FIG. 20C depicts a radial cross-section of system 620 at crest 626B ofsegment 626. Balloon 624 is in a crimped folded configuration with folds708 shown.

As balloon 622 inflates and expands the segments, the spacer clips applyforces on each segment which prevents movement of the segments away fromeach other due to shortening of the segments to maintain the gap width.

In some embodiments, segmented scaffolds may be coated with anantiproliferative drug. The spaces between the segments, in particularwhere there are balloon pillows, represent regions where there may be nodrug. If the pillowed regions were large, then there may be a potentialfor focal stenosis developing where the balloon pillows touched thevessel wall. Coating the balloon with an antiproliferative drug willdeliver the drug to the segment of the vessel wall. The drug can includepaclitaxel, protaxel, taxotere, docetaxel, ortataxel, everolimus,sirolimus, myolimus, novolimus, temsirolimus, merilimus, deforolimus, orzotarolimus. In some embodiments, the drug coating can be applied to theentire balloon surface. Alternatively, the coating can be limited to thegap regions between the segments. The coating can be applied using knowntechniques such as direct fluid application, spraying, brushing, ordipping. The coating can be applied prior to forming pre-pillows.Alternatively, the coating can be formed after formation of thepre-pillows to avoid potential damage to the balloon coating during thepre-pillow formation.

The coating can also be applied after mounting the scaffold segments onthe balloon. In this case, a coating can be applied to the scaffoldsegments as well. Alternatively, the coating can be selectively appliedonly to the gap regions of the balloon surface, for example, byshielding the scaffold segments during application. In anotherembodiment, the coating is applied to the entire working length of theballoon after formation of the pre-pillows, but before the scaffoldsegments are crimped on. The coating and drug applied to the gap regionsof the balloon surface may be different than the coating and drugapplied to the scaffold segments. The balloon coating can be appliedbefore the pre-crimping, between pre-crimping and final crimping, orafter final crimping.

The vessel regions between the segments can act as “hinge points” whenthe vessel bends and compresses, as there is no scaffold there. Hingepoints may be more likely to develop focal restenosis due to theexaggerated flexing and potential injury at the hinge point. Coating theballoon pillows with a drug coating may prevent restenosis at thesehinge points.

The coating on the balloon can be pure drug or a drug mixed with apolymeric carrier. The polymeric carrier can be bioresorbable polymer.Additional components may be present in the balloon coating includingradiopaque contrast agents, iopromide, iohexol, surfactants, Tween 80,Tween 60, Tween 40, emulsifiers, poly(vinyl pyrrolidonone), glycerol,propylene glycol, shellac, and urea. Tween 40, 60, 80 can be obtainedfrom Sigma-Aldrich. Tween 40 is polyoxyethylenesorbitan monopalmitate,Tween 60 is polyoxyethylene sorbitan monostearate, and Tween 80 ispolyethylene glycol sorbitan monooleate.

When the segments are deployed, the drug on the balloon in the gapsmakes contact with the vessel wall. At least some of the drug transfersto or adheres to the vessel wall and remains even after deflation andremoval of the balloon from the treatment site.

The scaffold segments of the present invention can be made from varietyof biodegradable polymers including, but not limited to, poly(L-lactide)(PLLA), polymandelide (PM), poly(DL-lactide) (PDLLA), polyglycolide(PGA), polycaprolactone (PCL), poly(trimethylene carbonate) (PTMC),polydioxanone (PDO), poly(4-hydroxy butyrate) (PHB), and poly(butylenesuccinate) (PBS). The scaffold segments can also be made from random andblock copolymers of the above polymers, in particular,poly(L-lactide-co-glycolide) (PLGA) and poly(L-Lactide-co-caprolactone)PLGA-PCL. The scaffold can also be made of a physical blending of theabove polymers. The scaffold segments can be made from PLGA includingany molar ratio of L-lactide (LLA) to glycolide (GA). In particular, thestent can be made from PLGA with a molar ratio of (LA:GA) including85:15 (or a range of 82:18 to 88:12), 95:5 (or a range of 93:7 to 97:3),or commercially available PLGA products identified as having these molarratios. High strength, semicrystalline polymers with a Tg above bodytemperature include PLLA, PGA, and PLGA.

“Radial strength” is the ability of a stent to resist radial compressiveforces, relates to a stent's radial yield strength and radial stiffnessaround a circumferential direction of the stent. A stent's “radial yieldstrength” or “radial strength” (for purposes of this application) may beunderstood as the compressive loading, which if exceeded, creates ayield stress condition resulting in the stent diameter not returning toits unloaded diameter, i.e., there is irrecoverable deformation of thestent. When the radial yield strength is exceeded the stent is expectedto yield more severely as only minimal additional force is required tocause major deformation. “Stress” refers to force per unit area, as inthe force acting through a small area within a plane. Stress can bedivided into components, normal and parallel to the plane, called normalstress and shear stress, respectively. Tensile stress, for example, is anormal component of stress applied that leads to expansion (increase inlength). In addition, compressive stress is a normal component of stressapplied to materials resulting in their compaction (decrease in length).Stress may result in deformation of a material, which refers to a changein length. “Expansion” or “compression” may be defined as the increaseor decrease in length of a sample of material when the sample issubjected to stress.

As used herein, the terms “axial” and “longitudinal” are usedinterchangeably and refer to a direction, orientation, or line that isparallel or substantially parallel to the central axis of a stent or thecentral axis of a tubular construct. The term “circumferential” refersto the direction along a circumference of the stent or tubularconstruct. The term “radial” refers to a direction, orientation, or linethat is perpendicular or substantially perpendicular to the central axisof the stent or the central axis of a tubular construct and is sometimesused to describe a circumferential property, i.e radial strength.

“Strain” refers to the amount of expansion or compression that occurs ina material at a given stress or load. Strain may be expressed as afraction or percentage of the original length, i.e., the change inlength divided by the original length. Strain, therefore, is positivefor expansion and negative for compression.

“Strength” refers to the maximum stress along an axis which a materialwill withstand prior to plastic deformation and then fracture. Theultimate strength is calculated from the maximum load applied during thetest divided by the original cross-sectional area.

“Modulus” may be defined as the ratio of a component of stress or forceper unit area applied to a material divided by the strain along an axisof applied force that result from the applied force. For example, amaterial has both a tensile and a compressive modulus.

The underlying structure or substrate of an implantable medical device,such as a stent can be completely or at least in part made from abiodegradable polymer or combination of biodegradable polymers, abiostable polymer or combination of biostable polymers, or a combinationof biodegradable and biostable polymers. Additionally, a polymer-basedcoating for a surface of a device can be a biodegradable polymer orcombination of biodegradable polymers, a biostable polymer orcombination of biostable polymers, or a combination of biodegradable andbiostable polymers.

EXAMPLES Example 1 Pillowed Balloon to Set Segment Spacing

FIG. 21A depicts a photograph of a delivery balloon in a deflated statewith pre-pillowed bands or sections to set scaffold segment spacing.

FIG. 21B depicts a close-up view of a pre-pillowed section. With thepre-pillowing of the balloon, the segments not only maintain aconsistent spacing during crimping, but also when deployed.

FIG. 22 illustrates the inflation process of a segmented scaffold thatshows that even segment spacing is maintained throughout expansion ofthe segments. The top picture shows a segmented scaffold crimped over adeflated balloon. The middle picture depicts the expansion when theballoon is partially inflated with the balloon having a dog bone shape.The ends of the balloon are inflated which partially expands thesegments at the ends. The center of the balloon is partially or notinflated. The bottom picture shows the completely inflated balloon andthe segments completely expanded. The balloon pre-pillowing maintains aneven segment to segment spacing. The pictures show that the segmentspacing increases during deployment, however, all spaces are the same.

Example 2 Animal Studies of Inflation of Balloon with Pre-PillowedSections

An animal study of the pre-pillowed balloon inflation with a segmentedscaffold was performed using a porcine model. A balloon withpre-pillowed sections with a segmented scaffold first inflated at theends creating a dog bone shape and then in the center of the balloon.The balloon shape change was observed by the contrasts shape underfluoroscopy. The final inflated balloon image showed even spacing of theimplanted scaffold segments.

FIG. 23A is a fluoroscopic image depicting implanted scaffold segments.FIG. 23A depicts the segmented scaffold implanted in the Right ExternalIliac in a porcine model. The even spacing of the radiopaque markers isshown by the arrows. The polymer scaffold does not show up underfluoroscopy so equal distance between markers signifies equal segmentspacing. FIG. 23B is a close-up view of a segment which shows theradiopaque markers.

Example 3 Pre-Crimping and Final Crimping of Scaffold Segments on aPre-Pillowed Balloon

FIG. 24A depicts scaffold segments placed on a stepped mandrel forloading into a pre-crimper.

FIG. 24B depicts pre-crimped segments of FIG. 24A upon removal from thepre-crimper.

FIG. 25A shows pre-crimped segments of FIG. 24B loaded onto apre-pillowed balloon.

FIG. 25B shows the finished crimped segments of FIG. 25A.

FIG. 25C is a close up view of the final crimped scaffold of FIG. 25Bshowing pillowing between the segments.

Example 4 Mechanical Test Results of Two Segmented Scaffold Designs

Mechanical tests were performed on two segmented scaffold designs. FIGS.26A-B depict flattened views of the two segmented scaffold designs. FIG.26A depicts a “square-diamond” design (“S1”) and FIG. 26B depicts a“tall diamond” design (“S2”). Line. A-A represents the cylindrical axisof the segments. FIG. 26A (“S1”) has a diamond structure that is closerto a square than the one shown in FIG. 26B (“S2”). The S2 segment has alarger diamond cell height, Hc, than the square diamond segment. It isbelieved that the S2 segment will undergo more plastic deformationduring crimping and then during expansion than the S1 segment.

The scaffold segments are laser cut from 7 mm expanded PLLA tubes. Thesegments have a 0.014 in strut width, 0.011 in strut radial thickness,and a 0.093 in crimped diameter. The properties of the scaffolds aregiven in Table 4.

TABLE 4 Properties of segmented scaffolds tested. Total Crimped Space atCrimped Scaf- Dia- Segment Segment 5.3 mm No. of Scaffold fold mondLength Space OD Seg- Length Design Shape (mm) (mm) (mm) ments (mm) S1Square 15.8 1.5 4.8 3 50 S2 Tall 14.7 0.5 5 3 45

The following functional characteristics of the two scaffolds weremeasured and compared with two scaffold designs that are non-segmented,NS1 and NS2. The non-segmented designs are similar to the design in FIG.1, which are composed of a plurality of zig-zag rings connected bylinks. The non-segmented scaffolds are made from PLLA tubes. Thefollowing properties were measured: dislodgement force, post dilate tofracture, diameter recoil, radial strength and stiffness, and crushrecovery.

FIG. 27 depicts the dislodgment force in lb_(f) for the four scaffolddesigns. The dislodgement force is the axial force required to axiallydislodge a crimped scaffold or segment off a balloon. The dislodgementforces for S1 and S2 are for the distal segment only.

FIG. 28 depicts the post dilate to fracture for the four scaffolddesigns. The post dilate to fracture is the diameter immediately priorto fracture (mm) when the crimped scaffold or scaffold segment isexpanded by the balloon.

FIG. 29 depicts the scaffold diameter recoil after deployment for thefour scaffold designs. Each scaffold is dilated to 6 mm by the balloon.The balloon is deflated, removing the radial outward force on thescaffolds. The removal of the radial outward force results in recoilinward of the scaffolds. The S1 and S2 designs have larger radii in thecorners which is believed to reduce the amount of plastic deformationand cracks. It is believed that the closed diamond pattern of S1 and S2tends to hold its shape better than an open zig-zag pattern.

FIG. 30 depicts the radial strength of the scaffold designs. The S2design is stronger in the radial direction. In general, the tightlypacked diamond shape is more than double the wider ring spaced zig-zagpatterns.

FIG. 31 depicts the radial stiffness of the scaffold designs.

FIG. 32 depicts the crush recovery of the scaffold designs. Thescaffolds were subjected to a pinching force which compresses thescaffolds to 50% of original diameter followed by release of the force.The crush recovery is the degree to which the scaffold recovered itsoriginal diameter.

Example 5 Animal Study Results for Implanted Segmented Scaffold Designs

Table 5 provides mean fracture counts for implanted segmented scaffoldsfor the S1 and S2 designs. The fracture counts were obtained fromexplanted scaffolds from a porcine model. The specimens were explanted28 days after implantation. The S1 and S2 designs are compared with twonon-segmented scaffold designs, NS1 and NS2. The S1 and S2 designsexhibited no strut discontinuities at 28 days post implant. The NS1 andNS2 designs had between 40 and 43 strut discontinuities in the same timeperiod.

TABLE 5 Mean fracture counts of scaffolds explanted from porcine modelafter 28 days. Mean Strut Fracture Count Design Ring Link Total S1 0.7 00.7 S2 0 0 0 NS1 38 5 43 NS2 36 4 40

Table 6 shows the late lumen loss of the S1 and S2 designs explantedfrom porcine model after 28 days along with results for thenon-segmented designs.

TABLE 6 Late lumen loss of scaffolds explanted from porcine model after28 days. Design Late Lumen Loss (mm) S1 1.02 S2 1.18 NS1 1.71 NS2 1.42

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

1-48. (canceled)
 49. A method, comprising: crimping a plurality ofscaffold segments to a balloon, wherein the crimped segments aredisconnected from each other and arranged end to end over the balloon;wherein ends of adjacent segments are separated by a gap having a gapsize, the balloon has an outer surface comprising a gap region locatedat the gap and the gap region has a width no greater than the gap size;and disposing a coating comprising an antiproliferative drug only at thegap region.
 50. The method of claim 49, wherein when the segments arecrimped to the balloon the gaps have a first size, when the segments areradially expanded by the balloon the gaps have a second size, andwherein the first size is equal to the second size.
 51. The method ofclaim 49, wherein the gap region comprises bands of raised balloonmaterial.
 52. A method, comprising: using a plurality of scaffoldsegments; using a balloon, the segments being crimped to the balloon,disconnected from each other and arranged end to end over the balloon,wherein ends of adjacent segments are separated by a gap having a gapsize; the balloon having an outer surface comprising a gap regionlocated at the gap and the gap region has a width no greater than thegap size; and attaching a spacer clip to the balloon outer surface atthe gap region by an adhesive or welding, the attached spacer clipcomprising: a portion in the gap region, and an arm comprising a hookadapted to engage a segment when the balloon is expanded so as torestrict movement of the segment relative to the portion when theballoon is inflated.
 53. The method of claim 52, further comprisingattaching a plurality of spacer clips, each having a first and secondarm disposed on opposite sides of the portion.
 54. A method, comprising:crimping a plurality of scaffold segments to a balloon, wherein thescaffolds are formed from a tube or sheet of polymer material, and thecrimped segments are disconnected from each other and arranged end toend over the balloon; and a segment of the segments comprising a firstring and a second ring adjoined to the first ring, and a link connectinga crest of the first ring to a trough of the second ring, and whereinthe plurality of rings are arranged to form diamond-shaped elements. 55.The method of claim 54, wherein the segments are separated by a gapregion, the method further comprising disposing a coating comprising anantiproliferative drug at the gap region.
 54. The method of claim 54,wherein the segment comprises a plurality of diamond-shaped elements.